Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001066891 | SCV001231914 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 1052 of the BRIP1 protein (p.Lys1052Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002320335 | SCV002608540 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-09 | criteria provided, single submitter | clinical testing | The p.K1052E variant (also known as c.3154A>G), located in coding exon 19 of the BRIP1 gene, results from an A to G substitution at nucleotide position 3154. The lysine at codon 1052 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |